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Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide

In this study, a novel scorpion venom‐derived peptide named Gonearrestide was identified in an in‐house constructed scorpion venom library through a combination of high‐throughput NGS transcriptome and MS/MS proteome platform. In total, 238 novel peptides were discovered from two scorpion species; a...

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Autores principales: Li, Bin, Lyu, Peng, Xi, Xinping, Ge, Lilin, Mahadevappa, Ravikiran, Shaw, Chris, Kwok, Hang Fai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111814/
https://www.ncbi.nlm.nih.gov/pubmed/29993185
http://dx.doi.org/10.1111/jcmm.13745
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author Li, Bin
Lyu, Peng
Xi, Xinping
Ge, Lilin
Mahadevappa, Ravikiran
Shaw, Chris
Kwok, Hang Fai
author_facet Li, Bin
Lyu, Peng
Xi, Xinping
Ge, Lilin
Mahadevappa, Ravikiran
Shaw, Chris
Kwok, Hang Fai
author_sort Li, Bin
collection PubMed
description In this study, a novel scorpion venom‐derived peptide named Gonearrestide was identified in an in‐house constructed scorpion venom library through a combination of high‐throughput NGS transcriptome and MS/MS proteome platform. In total, 238 novel peptides were discovered from two scorpion species; and 22 peptides were selected for further study after a battery of functional prediction analysis. Following a series of bioinformatics analysis alongside with in vitro biological functional screenings, Gonearrestide was found to be a highly potent anticancer peptide which acts on a broad spectrum of human cancer cells while causing few if any observed cytotoxic effects on epithelial cells and erythrocytes. We further investigated the precise anticancer mechanism of Gonearrestide by focusing on its effects on the colorectal cancer cell line, HCT116. NGS RNA sequencing was employed to obtain full gene expression profiles in HCT116 cells, cultured in the presence and absence of Gonearrestide, to dissect signalling pathway differences. Taken together the in vitro, in vivo and ex vivo validation studies, it was proven that Gonearrestide could inhibit the growth of primary colon cancer cells and solid tumours by triggering cell cycle arrest in G1 phase through inhibition of cyclin‐dependent kinases 4 (CDK4) and up‐regulate the expression of cell cycle regulators/inhibitors—cyclin D3, p27, and p21. Furthermore, prediction of signalling pathways and potential binding sites used by Gonearrestide are also presented in this study.
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spelling pubmed-61118142018-09-01 Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide Li, Bin Lyu, Peng Xi, Xinping Ge, Lilin Mahadevappa, Ravikiran Shaw, Chris Kwok, Hang Fai J Cell Mol Med Original Articles In this study, a novel scorpion venom‐derived peptide named Gonearrestide was identified in an in‐house constructed scorpion venom library through a combination of high‐throughput NGS transcriptome and MS/MS proteome platform. In total, 238 novel peptides were discovered from two scorpion species; and 22 peptides were selected for further study after a battery of functional prediction analysis. Following a series of bioinformatics analysis alongside with in vitro biological functional screenings, Gonearrestide was found to be a highly potent anticancer peptide which acts on a broad spectrum of human cancer cells while causing few if any observed cytotoxic effects on epithelial cells and erythrocytes. We further investigated the precise anticancer mechanism of Gonearrestide by focusing on its effects on the colorectal cancer cell line, HCT116. NGS RNA sequencing was employed to obtain full gene expression profiles in HCT116 cells, cultured in the presence and absence of Gonearrestide, to dissect signalling pathway differences. Taken together the in vitro, in vivo and ex vivo validation studies, it was proven that Gonearrestide could inhibit the growth of primary colon cancer cells and solid tumours by triggering cell cycle arrest in G1 phase through inhibition of cyclin‐dependent kinases 4 (CDK4) and up‐regulate the expression of cell cycle regulators/inhibitors—cyclin D3, p27, and p21. Furthermore, prediction of signalling pathways and potential binding sites used by Gonearrestide are also presented in this study. John Wiley and Sons Inc. 2018-07-11 2018-09 /pmc/articles/PMC6111814/ /pubmed/29993185 http://dx.doi.org/10.1111/jcmm.13745 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Li, Bin
Lyu, Peng
Xi, Xinping
Ge, Lilin
Mahadevappa, Ravikiran
Shaw, Chris
Kwok, Hang Fai
Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide
title Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide
title_full Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide
title_fullStr Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide
title_full_unstemmed Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide
title_short Triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—Gonearrestide
title_sort triggering of cancer cell cycle arrest by a novel scorpion venom‐derived peptide—gonearrestide
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111814/
https://www.ncbi.nlm.nih.gov/pubmed/29993185
http://dx.doi.org/10.1111/jcmm.13745
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